Variant chr9-128634895-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The ENST00000372715.7(DYNC2I2):c.1008C>T(p.Gly336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,612,834 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

DYNC2I2
ENST00000372715.7 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -2.58

Variant links:

Genes affected

DYNC2I2 (HGNC:28296): (dynein 2 intermediate chain 2) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Defects in this gene are a cause of short-rib thoracic dysplasia 11 with or without polydactyly. [provided by RefSeq, Mar 2014]

DYNC2I2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 9-128634895-G-A is Benign according to our data. Variant chr9-128634895-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 474843.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DYNC2I2	NM_052844.4 linkuse as main transcript	c.1008C>T	p.Gly336=	synonymous_variant	7/9	ENST00000372715.7	NP_443076.2
DYNC2I2	XM_047424057.1 linkuse as main transcript	c.1008C>T	p.Gly336=	synonymous_variant	8/10		XP_047280013.1
DYNC2I2	XM_011519179.3 linkuse as main transcript	c.924C>T	p.Gly308=	synonymous_variant	8/10		XP_011517481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2I2	ENST00000372715.7 linkuse as main transcript	c.1008C>T	p.Gly336=	synonymous_variant	7/9	1	NM_052844.4	ENSP00000361800	P1
DYNC2I2	ENST00000483181.1 linkuse as main transcript	n.601C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00111

AC:

169

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00135

AC:

334

AN:

247386

Hom.:

AF XY:

0.00129

AC XY:

174

AN XY:

134646

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.000698

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.000165

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00450

Gnomad NFE exome

AF:

0.00170

Gnomad OTH exome

AF:

0.000829

GnomAD4 exome

AF:

0.00131

AC:

1907

AN:

1460516

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

958

AN XY:

726580

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00389

Gnomad4 NFE exome

AF:

0.00142

Gnomad4 OTH exome

AF:

0.000829

GnomAD4 genome

AF:

0.00112

AC:

170

AN:

152318

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000740

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00137

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2024

Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. -

Short-rib thoracic dysplasia 11 with or without polydactyly

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.19

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.29

Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over